DESCRIPTION OF OVERALL CENTER (provided by applicant): The Harvard Digestive Diseases Center (HDDC) is a consortium of 63 independent investigators and 39 Associate Members with over $32 M annual research funding directly related to digestive diseases (34%NIDDK). The HDDC is focused on the cell biology and function of epithelial cells of the alimentary tract and the complex interactions of epithelia with the microbial flora and subepithelial cells of the lamina propria that result in mucosal immunity, allergy, innate host defense, digestion and absorption, the development of gastrointestinal neoplasia, and the many other functions of the Gl tract. Center Directors Drs. Wayne Lencer (PI) and Richard Blumberg (Co-PI) are scientific colleagues, Division Chiefs of Pediatric and Adult Gl at two major Harvard teaching hospitals, and leaders of NIH-funded training programs in Gastroenterology. The enrichment program includes an annual scientific symposium, a biannual regional conference "Frontiers in Mucosal Immunology", and two seminar series. The HDDC pilot-feasibility grant program is highly subscribed and competitive;the majority of previous awardees are now independently funded and still in digestive diseases-related research. A biostatistics resource supports translational/clinical research of HDDC members. The Imaging Core B provides advanced high-resolution light microscopy of fixed and live cells and tissues, and electron microscopy including EM tomography. The Epithelial Cell Biology Core C provides epithelial cell culture and transfection, microfluorimetry, electrophysiology, multi-color FACS, and multiplexed direct quantification of individual mRNAs. The Molecular and Cellular Biochemistry Core D provides protein and lipid purification and analysis and proteomic technologies. A new Gnotobiotics and Microbiology Core E provides access to germfree mouse isolators, stocks of germfree mice, microbiological assays, and a library of commensal and pathogen strains for use in the study of the gastrointestinal commensal flora and BL1 and BL2 pathogens. Our overarching mission is to foster and expand basic and translational science in digestive diseases by: 'connecting people, 'creating opportunity, and 'extending resources.